The extensive use of L-asparaginase in combination therapy makes it imperative to study the effect of L-Asn'ase, if any, on the utilization of other antineoplastic drugs by the cell. The effect of L-Asn'ase on the antileukemic action of methotrexate, cytosine arabinoside, 6- mercaptopurine, 5-flourouracil, prednisone and vincristine, and vice versa, will be studied in mouse leukemia. Various doses, order and time between L-Asn'ase and one other drug will be used. For Ara-C or 6-MP with L-Asn'ase, we will try protocols that come as close as possible to the six regimens used in Protocol #002 of Group A of the Children's Cancer Study, which also uses L-Asn'ase in combination with either drug. By comparing mice survival data with remission data on the patients, it may be possible to draw a correlation between relative rankings of equivalent protocols in mice and man. We will also study the feasibility of predicting responsiveness to L-Asn'ase treatment using the inhibition by L-Asn'ase of incorporation into glycoprotein of L-fucose and D-glucosamine as a test. This will be studied in various mouse leukemia cells with different degrees of responsiveness to L-Asn'ase. If this test proved to be meaningful, it will be extended to the limited number of children with leukemia who are admitted to the University of Rochester Medical Center and are candidates for L-Asn'ase therapy.